Journal
BIOMATERIALS
Volume 184, Issue -, Pages 31-40Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2018.09.001
Keywords
X-ray excited photodynamic therapy; FRET; Rear-earth nanoparticles; Deep-seated tumor therapy; Antitumor nanocomposite
Funding
- National Natural Science Foundation of China [31700865, 81771972]
- National Key Research and Development Program of China [2017YFC0107400, 2017YFC0107402, 2017YFC0107405, 2017YFC0107401, 2017YFC0107404, 2017YFC0107403]
- Natural Science Basic Research Plan in Shaanxi Province of China [2017JQ8049]
- State Key Laboratory of Cancer Biology Fund [CBSKL201706, CBSKL2017Z05]
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The limitation of light penetration depth invalidates the application of photodynamic therapy in deep-seated tumors. X-ray excited photodynamic therapy (X-PDT), which is based on X-rays excited luminescent nanoparticles (XLNP), provides a new strategy for PDT in deep tissues. However, the high X-ray dosage used and nonspecific cytotoxicity of the nanoparticle-photosensitizer nanocomposite (NPs-PS) hamper in-vivo X-PDT applications. To address these problems, a simple and efficient NPs-PS nanocomposite using beta-NaGdF4: Tb3+ nanoparticles and widely used PS called Rose Bengal (RB) was designed. With perfectly matched spectrum of NPs emission and RB absorption upon X-ray excitation and covalent conjugation of a large amount of RB on NP surfaces to minimize the energy transfer distance, the system demonstrated ultra-high FRET efficiency up to 99.739%, which leads to maximum production of singlet oxygen for PDT with significantly increased anti-tumor efficacy. By 2-aminoethylphosphonic acid surface modification of NPs, excellent biocompatibility was achieved even at a high concentration of 1 mg/mL. The m-vivo X-PDT efficacy was found around 90% of HepG2 tumor growth inhibition with X-ray dose of only 1.5 Gy, which shows the best anti-tumor efficacy at same X-ray dose level reported so far. The present work provides a promising platform for in-vivo X-PDT in deep tumors.
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